Relative Dose Intensity of Trabectedin and Outcome of Advanced L‐Sarcomas
ABSTRACT Background Trabectedin, which is approved for advanced soft tissue sarcoma management, has a complex mechanism of action, but can be classified as an alkylating agent. The need to maintain a high relative dose intensity (RDI) is not clearly established in this clinical setting. Methods We c...
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Wiley
2025-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.71131 |
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| author | Stephen Poitureau Marie‐Cécile Le Deley Mehdi Brahmi Emmanuelle Bompas Jean‐Emmanuel Kurtz Simon Nannini Christophe Perrin Loïc Lebellec Thomas Ryckewaert Redha Ould‐Ammar Clémence Leguillette Jean‐Yves Blay Nicolas Penel |
| author_facet | Stephen Poitureau Marie‐Cécile Le Deley Mehdi Brahmi Emmanuelle Bompas Jean‐Emmanuel Kurtz Simon Nannini Christophe Perrin Loïc Lebellec Thomas Ryckewaert Redha Ould‐Ammar Clémence Leguillette Jean‐Yves Blay Nicolas Penel |
| author_sort | Stephen Poitureau |
| collection | DOAJ |
| description | ABSTRACT Background Trabectedin, which is approved for advanced soft tissue sarcoma management, has a complex mechanism of action, but can be classified as an alkylating agent. The need to maintain a high relative dose intensity (RDI) is not clearly established in this clinical setting. Methods We conducted a retrospective study in five expert centers to compare the progression‐free survival (PFS) and overall survival (OS) of patients with advanced L‐Sarcomas (liposarcomas or leiomyosarcoma) according to the RDI calculated over the first three cycles (RDI < 80% and RDI ≥ 80%). Comparisons of patients' characteristics were done using Chi‐2, Fisher exact, and Wilcoxon tests. Associations between PFS/OS and RDI were estimated and tested in Cox models. Results Out of 332 patients treated with trabectedin between 09/1999 and 12/2021, 244 have received at least 3 cycles before progression. Among these 244 patients, the median RDI during the first 3 cycles was 83% (range, 48%–106%), the mean RDI was 81% (±14%) and 106 patients had RDI < 80%. An RDI < 80% was more frequently observed in patients treated in a center with a high volume of activity (82/169, 49%, vs. 24/75, 32%, p = 0.02), in patients who had previously received pazopanib (12/18, 67%, vs. 94/225, 42%, p = 0.04), and in patients who experienced grade 3 neutropenia during the first cycle (56/77, 73% vs. 35/127, 28%, p < 0.001). PFS did not significantly differ according to RDI (p = 0.08): HR(< 80%/≥ 80%) = 0.79 (95% CI, 0.61–1.03), median PFS = 8.4 months (7.0–9.3) when RDI < 80% vs. 5.9 months (4.4–6.8) when RDI ≥ 80%. We observed no significant difference in terms of OS (p = 0.53): HR(< 80%/≥ 80%) = 0.92 (95% CI, 0.70–1.20), median OS = 18.2 months (15.6–23.4) when RDI < 80% vs. 15.8 months (13.2–19.7) when RDI ≥ 80%. Conclusion This retrospective study does not support a link between high trabectedin RDI and PFS or OS for advanced L‐sarcoma patients. |
| format | Article |
| id | doaj-art-6c5d674b214047c2a30cbd0f0108d179 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj-art-6c5d674b214047c2a30cbd0f0108d1792025-08-26T10:58:44ZengWileyCancer Medicine2045-76342025-08-011416n/an/a10.1002/cam4.71131Relative Dose Intensity of Trabectedin and Outcome of Advanced L‐SarcomasStephen Poitureau0Marie‐Cécile Le Deley1Mehdi Brahmi2Emmanuelle Bompas3Jean‐Emmanuel Kurtz4Simon Nannini5Christophe Perrin6Loïc Lebellec7Thomas Ryckewaert8Redha Ould‐Ammar9Clémence Leguillette10Jean‐Yves Blay11Nicolas Penel12Lille University, Medical School Lille FranceDepartment of Clinical Research and Innovation Centre Oscar‐Lambret Lille FranceDepartment of Medical Oncology Centre Léon Bérard, University Claude Bernard Lyon I Lyon FranceDepartment of Medical Oncology Institut de Cancérologie de L'ouest Nantes FranceDepartment of Medical Oncology Institut de Cancérologie de Strasbourg‐Europe Strasbourg FranceDepartment of Medical Oncology Institut de Cancérologie de Strasbourg‐Europe Strasbourg FranceMedical Oncology Unit, Centre Eugène Marquis Rennes FranceDepartment of Medical Oncology Centre Oscar Lambret Lille FranceDepartment of Medical Oncology Centre Oscar Lambret Lille FranceDepartment of Clinical Research and Innovation Centre Oscar Lambret Lille FranceDepartment of Clinical Research and Innovation Centre Oscar Lambret Lille FranceDepartment of Medical Oncology Centre Léon Bérard, University Claude Bernard Lyon I Lyon FranceDepartment of Medical Oncology Centre Oscar‐Lambret Lille FranceABSTRACT Background Trabectedin, which is approved for advanced soft tissue sarcoma management, has a complex mechanism of action, but can be classified as an alkylating agent. The need to maintain a high relative dose intensity (RDI) is not clearly established in this clinical setting. Methods We conducted a retrospective study in five expert centers to compare the progression‐free survival (PFS) and overall survival (OS) of patients with advanced L‐Sarcomas (liposarcomas or leiomyosarcoma) according to the RDI calculated over the first three cycles (RDI < 80% and RDI ≥ 80%). Comparisons of patients' characteristics were done using Chi‐2, Fisher exact, and Wilcoxon tests. Associations between PFS/OS and RDI were estimated and tested in Cox models. Results Out of 332 patients treated with trabectedin between 09/1999 and 12/2021, 244 have received at least 3 cycles before progression. Among these 244 patients, the median RDI during the first 3 cycles was 83% (range, 48%–106%), the mean RDI was 81% (±14%) and 106 patients had RDI < 80%. An RDI < 80% was more frequently observed in patients treated in a center with a high volume of activity (82/169, 49%, vs. 24/75, 32%, p = 0.02), in patients who had previously received pazopanib (12/18, 67%, vs. 94/225, 42%, p = 0.04), and in patients who experienced grade 3 neutropenia during the first cycle (56/77, 73% vs. 35/127, 28%, p < 0.001). PFS did not significantly differ according to RDI (p = 0.08): HR(< 80%/≥ 80%) = 0.79 (95% CI, 0.61–1.03), median PFS = 8.4 months (7.0–9.3) when RDI < 80% vs. 5.9 months (4.4–6.8) when RDI ≥ 80%. We observed no significant difference in terms of OS (p = 0.53): HR(< 80%/≥ 80%) = 0.92 (95% CI, 0.70–1.20), median OS = 18.2 months (15.6–23.4) when RDI < 80% vs. 15.8 months (13.2–19.7) when RDI ≥ 80%. Conclusion This retrospective study does not support a link between high trabectedin RDI and PFS or OS for advanced L‐sarcoma patients.https://doi.org/10.1002/cam4.71131dose reductionrelative dose intensitysoft tissue sarcomatoxicitytrabectedin |
| spellingShingle | Stephen Poitureau Marie‐Cécile Le Deley Mehdi Brahmi Emmanuelle Bompas Jean‐Emmanuel Kurtz Simon Nannini Christophe Perrin Loïc Lebellec Thomas Ryckewaert Redha Ould‐Ammar Clémence Leguillette Jean‐Yves Blay Nicolas Penel Relative Dose Intensity of Trabectedin and Outcome of Advanced L‐Sarcomas Cancer Medicine dose reduction relative dose intensity soft tissue sarcoma toxicity trabectedin |
| title | Relative Dose Intensity of Trabectedin and Outcome of Advanced L‐Sarcomas |
| title_full | Relative Dose Intensity of Trabectedin and Outcome of Advanced L‐Sarcomas |
| title_fullStr | Relative Dose Intensity of Trabectedin and Outcome of Advanced L‐Sarcomas |
| title_full_unstemmed | Relative Dose Intensity of Trabectedin and Outcome of Advanced L‐Sarcomas |
| title_short | Relative Dose Intensity of Trabectedin and Outcome of Advanced L‐Sarcomas |
| title_sort | relative dose intensity of trabectedin and outcome of advanced l sarcomas |
| topic | dose reduction relative dose intensity soft tissue sarcoma toxicity trabectedin |
| url | https://doi.org/10.1002/cam4.71131 |
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